Dysphagia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Overview

Dysphagia can result from propulsive failure, motility disorders, structural disorders, intrinsic or extrinsic compression of the oropharynx or esophagus. Propulsive failure can result from dysfunction of the central nervous system control mechanisms, intrinsic musculature, or peripheral nerves. Structural abnormalities may result from surgery, neoplasm, caustic injury, or congenital anomalies.

Pathophysiology

Physiology of normal swallowing

Normal physiology of swallowing can discussed under three phases:

Oral phase

• Preparatory phase:
  • Preparatory phase involves mastication and formation of a bolus in the oral cavity.
• Voluntary phase:
  • Voluntary phase is characterized by propelling the bolus into the pharyngeal phase.
  • Voluntary phase is controlled by
    • Corticobulbar tracts
    • Cranial nerves V, VII, and XII.
• Pharyngeal phase:
  • Pharyngeal phase is a reflex mechanism and is controlled by the cranial nerves V, X, XI, and XII.
• Esophageal phase:
  • Once the bolus reaches esophageal phase, esophagus is responsible for moving the bolus along the upper gastrointestinal tract to initiate the process of digestion by delivering it to stomach.
  • The esophagus has anti-reflux barrier which prevents the return of the acidic contents of the stomach back to the esophagus.
  • The anti-reflux barrier is formed by the lower esophageal sphincter (LES) and a part of the diaphragm.
  • The lower esophageal sphincter is contracting smooth muscle located at the end of the esophagus.
  • Due to it's high pressure tone LES, acts as a strong barrier between the esophagus and the stomach contents.

Pathogenesis of physiological dysphagia

Physiological dysphagia occurs as a result of normal aging. Normal aging results in certain changes that affect the swallowing mechanism which include:

• Reduced lingual movement.
• Delayed onset of the pharyngeal swallow.
• Delayed upper esophageal sphincter relaxation during swallowing.
• Diminished pharyngo-laryngeal response.
• Decreased nerve function.
• Decline in muscle mass.

Pathogenesis of pathological dysphagia

Pathological dysphagia can occur as a result of the following mechanisms.

1. Luminal Stenosis

• Esophageal lumen can be narrowed by the following factors:\
  • Stricture
  • Inflammation
  • Esophageal webs
  • Malignancy

2. Non-obstructing gastro-esophageal disease

• Majority of the patients that present with dysphagia will have normal investigation findings.
• Normal findings suggests a somato-sensory dysfunction rather than neuro-muscular cause of dysphagia.
• Non-obstructive causes of dysphagia include:
  • Motility disorders of esophagus
  • Rheumatological conditions
  • Medication induced dysphagia
  • Neurological disorders

Motility disorders of esophagus

• Motility disorder of esophagus occurs when there is an imbalance between inhibitory and excitatory neurons of the myenteric plexus at the distal esophageal sphincter.
• This imbalance results in a decrement of inhibitory innervation leading to aperistalsis.
• Reduced inhibitory innervation also leads to failure of relaxation of the lower esophageal sphincter resulting in difficulty in swallowing (dysphagia).

Rheumatological conditions

• The smooth muscle of the mid and lower esophagus is replaced by fibrous tissue secondary to the underlying autoimmune pathology leading to incompetence of the lower esophageal sphincter (LES) and subsequently to GERD and dysphagia.

• Most common rheumatological conditions associated with dysphagia include:
  • CREST syndrome
  • Sjogren’s syndrome
  • Systemic lupus erythematosus (SLE)
  • Mixed connective tissue disease (MCTD)
  • Rheumatoid arthritis

Medication induced

• Medications can contribute to dysphagia by making peristalsis difficult either by:
  • Decreasing the strength of lower esophageal sphincter relaxation.
  • Reducing the lubrication of esophageal lumen by decreasing the salivary secretions.
• Some medications also have a local or systemic immunosuppressant effect can predispose to infective oesophagitis.
  • Antipsychotics,
  • Tricyclic antidepressant
  • Anticholinergic
  • Opioids
  • Iron supplements
  • Potassium supplements
  • NSAIDs
  • Tetracyclines
  • Macrolides
  • Bisphosphonates
  • Calcium channel blockers
  • Nitrates
  • Alcohol
  • Theophylline

Neurological disorders

• Neurological disorders predominanlty affect the oropharyngeal phase.
• Nerves that weakness of the oral musculature and tongue movements resulting in failure to form a intact food bolus and decreased sensitivity of the pharyngeal receptors, subsequent to neurological compromise.
• The central, autonomic or peripheral nervous system is affected by several neurological diseases such as:
  • Parkinsons disease
  • Myasthenia gravis
  • Motor neuron disease
  • Cerebrovascular accident
  • Multiple sclerosis

• Dysphagia is commonly seen after stroke affecting the basal ganglia and the cortex, as it affects the ability to initiate the swallow and decrement in bolus transit between pharynx and esophagus.

The following table summarizes the mechanism, genetic association, gross pathology features and microscopic findings of common causes of dysphagia.

Cause of dysphagia	Type of food		Type of progression	Pathophysiological changes	Genetic association	Gross pathology features	Microscopic findings
Oropharyngeal dysphagia	Soilds	Liquids	Intermittent/Progressive
•Zenker's diverticulum •Webs	Yes	No	Progressive	•Zenker's diverticulum(ZD): It is the result of motor abnormalities of the esophagus ZD is a defect over the Killian's triangle, a point of weakness in the muscular wall of the hypopharynx Killian's triangle is surrounded by the cricopharyngeal sphincter and oblique fibers of the inferior constrictor of the pharyngeal muscle.  ZD should be considered a pseudodiverticulum as it includes only mucosa and submucosa.		Diverticulum or a sac is seen in the esophagus	Pseudo diverticulum Only mucosa and submucosa present Chronic submucosal inflammation Epithelial atypia or dysplasia
				•Webs
•Neoplasm	Yes	Yes	Progressive	•Neoplasm
Myogenic causes •Myasthenia gravis •Connective tissue disorder •Myotonic dystrophy Neurogenic causes •ALS •Parkinsonism •Stroke	Yes	Yes	Progressive
Esophageal dysphagia
•Pill esophagitis •Caustic injury •Chemotherapy	Yes	No
•Strictures •Esophageal Cancer	Yes	No	Progressive	Esophageal stricture is the result of: Lower pressure of esophageal sphincter in gastroesophageal reflux disease Esophageal motor disorders Inflammation and fibrosis due to intrinsic diseases of esophagus, such asneoplasia Surgical esophageal anastomosis Esophageal compression by other organs	The following genes can be involved: ACD CTC1 DKC1 NHP2 NOP10 PARN RTEL1 TERC TERT TINF2 WRAP53	On gross pathology, circumferential thickening of the lower esophageal wall are characteristic finding of esophageal stricture due to gastroesophageal reflux disease. Pale mucosa with white exudate in lymphocytic esophagitis Swelling and hemorrhagic congestion in caustic ingestion Multiple yellow plaques in infectious esophagitis due to Candida Ulceration of the esophagus in viral esophagitis	On microscopic histopathological analysis, characteristic findings of esophageal stricture due to gastroesophageal reflux disease are: Intraepithelial lymphocytosis Basal cell hyperplasia Ulceration
				•Esophageal Cancer:	Mutations in the following genes can cause esophageal cancer: Chromosomal losses (4q, 5q, 9p, and 18q) Chromosomal gains (8q, 17q, and 20q) Gene amplifications (7, 8, and 17q) PT53 genes and P16 genes  Variants in ADH and/or ALDH2 genes	Squamous cell carcinoma or adenocarcinoma of the esophagus may appear as: Flat and irregular plaque Polypoid lesion  Ulcerating, fungating mass. Location: Squamous cell carcinoma is usually found in the mid-third of the esophagus. Adenocarcinoma is usually found in the lower third of the esophagus near the gastric opening.	Nuclear atypia of malignancy: Found in both types: Poikilocytosis Anisocytosis Staining variation Mitotic activity
•Rings •Webs	Yes	No	Intermittent	Rings: Webs: Multiple theories have been found: Webs may form due to the chronic damage to the esophageal mucosa Or due to failure of the esophagus to recanalize.
•Achalasia •Diffuse esophageal spasm(DES)	Yes	Yes	Intermittent	•Achalasia: Pathological examination reveals a defect in the nerves that control the motility of the esophagus (the myenteric plexus).  The esophagus is dilated and hypertrophied.	HLA class II moleculesVasoactive intestinal peptide KIT Interleukin 23 receptor|	There is defect in the nerves that control the motility of the esophagus (the myenteric plexus).  The esophagus is dilated and hypertrophied.
				•Diffuse esophageal spasm(DES): Impairment of inhibitory myenteric plexus neurons Dysregulation of endogenous NO synthesis or/and degradation	There is a genetic association between DES and achalasia	Gross thickening of muscularis propria layer and lower esophageal sphincter (LES) due to hyperplasia are characteristic findings of DES	There is degeneration of vagal fibres, inflammatory infiltration of myenteric plexus, and hyperplasia of smooth muscles are characteristic findings of DES
•Scleroderma	Yes	Yes	Progressive

Gallery

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Zenkers diverticulum

Zenkers diverticulumSource: Libre Pathology

Esophageal cancer

Esophageal squamous cell carcinoma by Nephron - Own work BY-SA 3.0

Esophageal adenocarcinoma by Nephron - Own work, CC BY-SA 3.0

Esophagitis

H&E stain of esophagus biopsy showing eosinophilic esophagitis, manifested by an infiltration of eosinophils in the lamina propria

Esophageal stricture

Esophageal stricture <"https://commons.wikimedia.org/wiki/File%3ATinci%C3%B3n_hematoxilina-eosina.jpg"> via Wikimedia Commons</ref>

Esophageal stricture due to GERD, via wikipedia.org